Chengyi Li

Direct Solvent-Derived Polymer-Coated Nitrogen-Doped Carbon Nanodots with High Water Solubility for Targeted Fluorescence Imaging of Glioma

Cancer imaging requires biocompatible and bright contrast-agents with selective and high accumulation in the tumor region but low uptake in normal tissues. Herein, 1-methyl-2-pyrrolidinone (NMP)-derived polymer-coated nitrogen-doped carbon nanodots (pN-CNDs) with a particle size in the range of 5-15 nm are prepared by a facile direct solvothermal reaction. The as-prepared pN-CNDs exhibit stable and adjustable fluorescence and excellent water solubility. Results of a cell viability test (CCK-8) and histology analysis both demonstrate that the pN-CNDs have no obvious cytotoxicity. Most importantly, the pN-CNDs can expediently enter glioma cells in vitro and also mediate glioma fluorescence imaging in vivo with good contrast via elevated passive targeting.

Receptor-Mediated Drug Delivery Systems Targeting to Glioma

Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications.

Aptavalve-gated mesoporous carbon nanospheres image cellular mucin and provide on-demand targeted drug delivery

In this report, we present a mesoporous carbon nanosphere that can target drugs to tumors and image tumor biomarkers. A single-strand DNA (P0 aptamer) aptavalve was capped on the surface of doxorubicin-loaded oxide mesoporous carbon nanospheres (Dox-OMCN-P0) through π-π stacking for real-time imaging-guided on-demand targeting drug delivery. The Dox-OMCN-P0 could not only realize the detection of MUC1 tumor marker with a wide linear range (0.1 - 10.6 μmol/L) and a low detection limit (17.5 nmol) based on different apparatuses, but also achieve in-situ targeting imaging of cellular MUC1 concentration in vitro and in vivo via “off-on” fluorescence biosensing. Much attractively, as a real-time feedback of the diagnostic/imaging outcomes, Dox-OMCN-P0 accomplished the on-demand targeting drug delivery in quantitative response to MUC1. Controllable chemotherapy with sustained release and pH-sensitiveness, together with the potential photothermal therapy, were also clearly demonstrated. This is a simple but advanced platform, which could well achieve the real-time switchable imaging of cellular mucin for targeting cancer therapy.

Highly Crystalline Multicolor Carbon Nanodots for Dual-Modal Imaging-Guided Photothermal Therapy of Glioma

Imaging-guided site-specific photothermal therapy (PTT) of glioma and other tumors in central nervous system presents a great challenge for the current nanomaterial design. Herein, an in situ solid-state transformation method was developed for the preparation of multicolor highly crystalline carbon nanodots (HCCDs). The synthesis yields 6-8 nm-sized HCCDs containing a highly crystalline carbon nanocore and a hydrophilic surface, which therefore simultaneously provide strong photoacoustic and photothermal performances as well as tunable fluorescence emission. In vitro and in vivo results demonstrate that the novel HCCDs have high water dispersity and good biocompatibility, but potent tumor cell killing upon near-infrared irradiation. As demonstrated in U87 glioma-bearing mice, HCCDs specifically accumulate in brain tumors and facilitate dual-modal imaging-guided PTT, with therapeutic antitumoral effects without any apparent damage to normal tissues.

Glioma targeted delivery systems

Abstract Glioma has been considered to be the most frequent primary tumor within central nervous system (CNS). The complexity of glioma, especially the existence of blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on the standard therapy (surgery combined with radiotherapy or chemotherapy). This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. Besides, adsorptive-mediated, transporter-mediated process, or nasal pathway are also widely studied strategies. This review will summarize recent progresses on glioma targeted drug delivery systems based on several main mechanisms and conclude the challenges and prospects of these glioma targeted systems for future applications.

Facile marriage of Gd3+ to polymer-coated carbon nanodots with enhanced biocompatibility for targeted MR/fluorescence imaging of glioma

Illustration of the facile to prepare NCDDG (A) and NCDDG (B) and Fate of NCDDG (G) administrated intravenously in vivo and its biological effects. ABSTRACT Overcoming blood‐brain barrier (BBB) for precise glioma diagnosis remains an urgent challenge due to its peculiar location in central nervous system (CNS). Herein, polymer‐coated carbon nanodots with high hydrophilicity were facilely married with Gd‐DTPA to construct a dual‐modal imaging system (NCDDG). This system was demonstrated with obviously decreased toxicity and enhanced magnetic resonance imaging (MRI) ability compared to traditional Gd‐DTPA. Meanwhile, NCDDG reserved the bright fluorescence of biocompatible carbon nanodots with increased spatial resolution. Attributed to small size and hydrophilic polymer coating, NCDDG was capable of overcoming the BBB and permeating leaky microvascular walls into surrounding glioma tissues via prolonged in vivo circulation and enhanced retention effect. As a result, dual1‐modal targeted MR/fluorescence imaging of glioma was synergistically achieved with high sensitivity and resolution. This work promised a potential contrast agent for sensitive clinical diagnosis of glioma.

Side effects-avoided theranostics achieved by biodegradable magnetic silica-sealed mesoporous polymer-drug with ultralow leakage

The development of drug delivery vehicles without side effects to normal physiological tissues represents an urgent challenge for safety and effective nanomedicine. Herein, a multifunctional drug delivery vehicle with ultralow leakage was presented, containing an ordered mesoporous resin as a polymer core and homogeneous Fe nanodots-doped silica as the biodegradable shell. In this core-shell structure, the Fe-doped silica shell acts as a compact inorganic cap to seal doxorubicin into the mesoporous polymer cores, but also serves as a superparamagnetic agent for magnetic targeting and magnetic resonance imaging (MRI). Importantly, the caps can be opened via Fe extraction-induced degradation to slowly release the loaded drug under the acidic tumor environment, while achieving ultralow drug leakage under normal in vivo blood circulation (physiological environment). This unique core-shell nanospheres with ultralow drug leakage were demonstrated to achieve side effects-avoided targeting chemotherapy guided by MRI with improved therapeutic outcomes, which showing great potential for efficient cancer theranostics.